Progress has been made toward the development of a trivalent live attenuated virus vaccine consisting of (1) a respiratory syncytial virus (RSV) subgroup A component; (2) an RSV subgroup B component; and (3) a parainfluenza virus type 3 (PIV3) vaccine component. The RSV A2 subgroup A candidate cpts248/404 was found to be satisfactorily attenuated, phenotypically stable, poorly transmissible, and immunogenic in seronegative infants and children over the age of six months. The cpts248/404 vaccine candidate retained some residual mild reactogenicity for the upper respiratory tract of young infants and a more attenuated derivative will need to be generated. However, the cpts248/404 virus did not cause fever, otitis media, pneumonia or bronchiolitis in young infants so we are close to achieving the level of attenuation needed for this target age group. Young infants infected with vaccine virus developed an immune response sufficient to restrict replication of a second dose of vaccine. The candidate vaccine was, for the most part, phenotypically stable. The development of an IgA response to the RSV G glycoprotein correlated with resistance to a second dose of vaccine. Thus, young infants can develop a protective immune response following infection with the live attenuated vaccine candidate that is effective against RSV, albeit an attenuated version of RSV. A recombinant virus bearing the cpts248/404 mutations plus a deletion of the SH gene had the same level of replication as the cpts248/404 mutant in seronegative vaccinees 6-24 months of age and was not studied in the 1-2 month old infant. More attenuated derivatives containing an additional ts mutation will be evaluated this year. The RSV subgroup B candidate vaccine, RSV B1 cp23, was found to be under- attenuated for use in fully susceptible infants and children and for this reason will not be pursued further. RSV subgroup B vaccines of the future will undoubtedly be antigenic chimeric recombinant viruses derived from cDNA encoding the RSV subgroup B F and G protective antigens on a background of an attenuated subgroup A virus. Such viruses have been made and clinical studies will be initiated this year.A live attenuated PIV3 candidate vaccine, JS cp45, produced by our CRADA partner, Wyeth-Lederle-Praxis, in qualified Vero cells is satisfactorily attenuated, phenotypically stable, poorly transmissible, and immunogenic in seronegative infants and children, as well as one month old infants. Immunity to a second dose was observed in the very young infant. Phase II trials have been initiated. - respiratory syncytial virus, parainfluenza virus, croup, pneumonia, bronchiolitis, vaccines, live-attenuated vaccines - Human Subjects